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Biomedical subjects

Toshio Fujisawa

Publications and source records attributed to Toshio Fujisawa.

9 recordsLinked to original sources
PubMed2026

Current Management of Primary Sclerosing Cholangitis (PSC) ~A Proposal for Early-stage PSC~.

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholangiopathy characterized by inflammation and fibrosis of intrahepatic and/or extrahepatic bile ducts. Its pathogenesis remains incompletely understood, and liver transplantation is currently the only curative treatment available. The diagnosis remains challenging, and no disease-specific biomarkers have been established. Recently, anti-integrin αvβ6 antibodies have emerged as promising serological biomarkers with high specificity for PSC. Advances in imaging modalities, including magnetic resonance cholangiopancreatography and peroral cholangioscopy, have improved diagnostic accuracy for PSC. Although various therapeutic approaches have been investigated, no treatment has been shown to improve the long-term outcomes. Microbiota-targeted therapies represent a promising emerging strategy. The clinical course of PSC, particularly in its early stages, is poorly defined. We propose a definition of early stage PSC consisting of two subtypes: small-duct PSC without liver fibrosis and large-duct PSC without cholestatic enzyme elevation or biliary strictures. Early intervention at this stage may improve the prognosis, thus highlighting the need for further validation.

Primary sclerosing cholangitis↗
PubMed2026

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p&#x2009;<&#x2009;0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p&#x2009;<&#x2009;0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p&#x2009;=&#x2009;0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans↗
PubMed2006

Inhibition of peroxisome proliferator-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties.

Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.

Actins↗
PubMed2006

Predominant T helper type 2-inflammatory responses promote murine colon cancers.

Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-gamma) gene deficient (-/-) [Th2 dominant] or interleukin (IL)-4(-/-) [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty-three weeks after initial treatment, the total colon was examined. When IFN-gamma(-/-) mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 +/- 1.7) than in WT (3.3 +/- 2.9) or IL-4(-/-) (3.1 +/- 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-gamma(-/-) mice than in IL-4(-/-) mice. Histologically, the tumors were well- or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-gamma(-/-) mice showed distinct nuclear expression of beta-catenin, in contrast to the strong membrane staining seen in tumors of IL-4(-/-) mice. In conclusion, colonic inflammation associated with Th2-dominant cytokine responses enhanced the formation of malignant neoplasms.

Adenocarcinoma↗
PubMed2006

[Clinical features of long time survivors with unresectable pancreatic cancer treated by gemcitabine alone].

The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine (GEM) alone and to predict survival time after the first course of treatment. Eighteen consecutive patients (median age 65.3 years, range 49-77 years; 12 males, 6 females) with unresectable pancreatic cancer and a baseline Karnofsky's performance state = or >60 were treated with GEM in a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest until progression. The overall response rate was 0% (CR 0, PR 0, SD 11 cases, and PD 5 cases), and the median survival time (MST) was 268 days. We observed a statistically significant difference in the patients with or without liver metastasis at the start of treatment (131.6 vs 324.9 days; p=0.0045). We also evaluated the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with unresectable pancreatic cancer receiving GEM alone. We classified two subgroups into responders (patients with a decrease of = or >10% of the baseline CA 19-9 level after 4 weeks of chemotherapy) and non-responder (patients with a increase of the baseline CA 19-9 level or with a decrease of <10% of the baseline CA 19-9 level after 4 weeks of chemotherapy). Responder had a significantly better median survival than non-responders (416.6 vs 138.3 days; p=0.009). In conclusion, CA 19-9 serum concentration serves as an early indicator of response to chemotherapy with GEM alone in unresectable pancreatic cancer.

Adenocarcinoma↗
PubMed2005

Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10(-6) M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.

Animals↗
PubMed2003

[A case of mediastinal metastasis of renal small cell carcinoma, performing CHOP therapy for an acute respiratory failure by the air way obstruction under the mechanical ventilation].

A case of mediastinal metastasis of renal small cell carcinoma was reported. A 45-year-old female was admitted to our hospital complaining of worsening dyspnea. The chest radiograph and CT showed stenosis of the bronchi bilaterally due to the mediastinal mass. Prior to pathological diagnosis, CHOP therapy with cyclophosphamide, adriamycin, vincristine and prednisolone was performed under mechanical ventilation for the purpose of resuscitation. The therapy was effective; and the was weaned from the mechanical ventilator, resulting in complete remission. Transbronchial samples from the left main bronchus confirmed that the mediastinal mass was identical pathologically to the renal small cell carcinoma (RSCC) resected 5 years before. As a result, the mediastinal mass was diagnosed as a metastatic focus of RSCC. RSCC is known to have one of the most unfavorable prognoses among malignancies. Despite efforts with chemotherapy, almost all cases that appear in the literature died within 1 year after diagnosis. No standard treatment modality has yet been established. Thus, the present case is rare because an RSCC relapse after a long free period went into remission as a result of CHOP therapy. It is suggested that CHOP therapy may well be an effective tool against RSCC, and could be a valuable choice for a treatment regimen.

Acute Disease↗